HFO‐1234yf as a CF₃‐Building Block: Synthesis and Chemistry of CF₃‐Ynones

Abstract

Reaction of low cost, readily available 4 th generation refrigerant gas 2,3,3,3-tetrafluoropropene (HFO-1234yf) with lithium diisopropylamide (LDA) leads to formation of lithium 3,3,3-trifluoropropynide, addition of which to a range of aldehydes formed CF 3-alkynyl alcohol derivatives on multigram scale, which were oxidised using Dess-Martin periodinane (DMP) to give substituted CF 3-ynones with minimal purification required. Michael-type additions of alcohol and amine nucleo-[a] B.

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

“…In order to explore other nucleophiles, we employed 1,3-diketones, such as 5-methylhexane-1,3-dione and 5,5-dimethylhexane-1,3-dione (that is, one of the two methyl groups in acetylacetone was formally substituted for an isopropyl or a t -Bu moiety, respectively), but no reaction was observed at all. The conjugate addition of amines to this type of ynone has already been reported [ 21 ], where the authors pointed out the significant slowdown of the reaction rate when tert -butylamine was employed, which was considered to be a reflection of the sensitivity of ynones 2 towards steric hindrance.…”

“…This process allowed us to obtain the required ynones 2 as long as the residue R was aromatic, while with an aliphatic substituent in this position, a full conversion was not observed even after a prolonged reaction period and at a higher temperature, and such conditions seemed to evoke the degradation of the products 2 to some extent. This was not the case for the Dess–Martin periodinane oxidation and the propargylic alcohols with C 7 H 15 as the residue R 1 by Hoye et al [ 15 ] and C 9 H 19 as the residue R 1 by the Sandford group [ 21 ], who recorded 80% and 76% isolated yield, respectively, of the corresponding ketones. Because these compounds were previously isolated inconveniently by preparative GLC [ 15 ] or distillation [ 17 , 19 ], we decided to employ them without further purification.…”

“…Recently, we turned our attention to oxidized propargyl alcohols, namely ynones 2 , because of the interesting structure with two strongly electron-withdrawing moieties, resulting in a high electrophilicity. However, only a few methods have been reported thus far for their preparation [ 15 – 20 ], including one that appeared in 2020 [ 21 ]. However, they suffer from problems, such as the formation of the desired product 2 only as regioisomeric mixtures [ 15 , 17 ] or the applicability to only one substrate without any extension to other related compounds [ 16 , 18 – 20 ]…”

“…Aromatic and heteroaromatic compounds are recognized as useful intermediates, and as pointed out above, the expected high electrophilicity of 2 was considered to allow the utilization as efficient Michael acceptors. Actually, this was the case, and the Sandford group clarified the high potency of these compounds for the conjugate addition of N- as well as O-nucleophiles [ 21 ]. On the basis of such an idea, we tried two routes to gain access to 1) 4-substituted 6-(trifluoromethyl)salicylate derivatives (C-nucleophiles) and 2) 6-substituted 4-(trifluoromethyl)pyrimidines (N-nucleophiles), both in a concise fashion, with the full details, including the preparation of 2 , being reported herein.…”

Application of Industrially Relevant HydroFluoroOlefin (HFO) Gases in Organic Syntheses

“…In 2020, Sandford and co-workers reported a new method to produce CF 3 -ynones 32 from 2,3,3,3-tetrafluoroprop-1-ene (12) and demonstrated its importance by the synthesis of the anti-inflammatory drug celecoxib (34, Scheme 4). 18 In the first step of the sequence, 3,3,3-trifluoroprop-1ynyllithium (30) was generated from 12 using lithium diisopropylamide in MTBE at -10 °C. The formation of intermediate 30 was observed by NMR spectroscopy quenching the reaction mixture with H 2 O or D 2 O.…”